ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.5219G>A (p.Trp1740Ter)

dbSNP: rs137854219
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000388680 SCV000330441 pathogenic not provided 2016-04-19 criteria provided, single submitter clinical testing The W1740X nonsense variant in the TSC2 gene has been reported previously in association with tuberous sclerosis complex (TSC) (TSC2 LOVD). Additionally, a different nucleotide substitution, c.5220 G>A, resulting in the same nonsense variant has also been reported in association with TSC (Roberts et al., 2002). The W1740X variant is predicted to cause loss of normal protein function through protein truncation as the last 68 amino acids of the tuberin protein are lost. Therefore, the presence of W1740X is consistent with a diagnosis of TSC
Invitae RCV001852882 SCV002236315 pathogenic Tuberous sclerosis 2 2021-05-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the TSC2 protein. Other variant(s) that disrupt this region (p.Arg1745Glnfs*27) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This nonsense change has been observed in individual(s) with clinical features of tuberous sclerosis complex (PMID: 31856217, 12136241). ClinVar contains an entry for this variant (Variation ID: 49362). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp1740*) in the TSC2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 68 amino acid(s) of the TSC2 protein.
Tuberous sclerosis database (TSC2) RCV000042622 SCV000066416 not provided Tuberous sclerosis syndrome no assertion provided curation

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